Cancer is the overall leading cause of death. At present, the primary form of cancer treatment technique is surgical treatment, which is carried out in combination with radiation treatment and chemotherapy. In spite of the development of novel surgical techniques and the discovery of novel anticancer agents of recent years, outcomes from cancer treatment still remain unimproved, except in the cases of some types of cancer. In recent years, cancer antigens recognized by cytotoxic T cells that are reactive to cancer and genes encoding cancer antigens have been identified along with the development of molecular biology and cancer immunology, and expectations for antigen-specific immunotherapy have increased (Tsuyoshi Akiyoshi, Gan to Kagaku Ryouhou (Cancer and Chemotherapy), 1997, vol. 24, pp. 551-519, Cancer and Chemotherapy Publishers Inc., Japan).
Immunotherapy requires the cancer-cell-specific presence of a peptide, polypeptide, or protein that is recognized as a target antigen, as well as substantial absence thereof in normal cells from the viewpoint of alleviation of side effects. In 1991, Boon et al. (the Ludwig Institute for Cancer Research, Belgium) isolated the human melanoma antigen MAGE1 recognized by the CD8+ T cell via cDNA expression cloning using an autologous cancer cell line and cancer-reactive T cells (Bruggen P. et al., Science, 254: 1643-1647, 1991). Thereafter, the SEREX (serological identifications of antigens by recombinant expression cloning) method, which identifies the tumor antigen recognized by the antibody produced in response to autologous cancer in the body of a cancer patient via gene expression cloning was reported (Proc. Natl. Acad. Sci. U.S.A., 92: 11810-11813, 1995; and U.S. Pat. No. 5,698,396). Some cancer antigens have been isolated by such techniques (Int. J. Cancer, 72: 965-971, 1997; Cancer Res., 58: 1034-1041, 1998; Int. J. Cancer, 29: 652-658, 1998; Int. J. Oncol., 14: 703-708, 1999; Cancer Res., 56: 4766-4772, 1996; and Hum. Mol. Genet. 6: 33-39, 1997). In addition, clinical testing of cancer immunotherapy targeting some such antigitens has been initiated.
As in the case of humans, dogs and cats are known to suffer from a variety of tumors, such as mammary gland cancer, leukemia, and lymphoma, and tumors are highly ranked in statistics for canine or feline diseases. However, there are no effective therapeutic, preventive, or diagnostic agents for canine or feline cancer at present. Most dog or cat owners would not notice canine or feline tumors until tumors become advanced and enlarged. Even if tumors are removed via surgical operation or drugs for human use (e.g., anticancer drugs) are administered, tumors are often already beyond cure, and animals often die shortly after treatment. Under such circumstances, if therapeutic, preventive, and diagnostic agents for cancer that are effective for dogs or cats become available, application thereof for canine or feline cancer can be expected.
The cytoplasmic and proliferation-associated protein 1 (CAPRIN-1) is expressed when dormant normal cells are activated or undergo cell division. CAPRIN-1 is an intracellular protein that is known to form intracellular stress granules with RNA in the cell and to be associated with regulation of mRNA transportation and translation. CAPRIN-1 is also known by various other names, and examples thereof include the GPI-anchored membrane protein 1 and the membrane component surface marker 1 protein (M11S1). CAPRIN-1 has names that convey the impression that it has been known as a cell membrane protein. Such other names derive from a report to the effect that the CAPRIN-1 gene sequence has a GPI-binding region and it is a membrane protein expressed in a large-intestine-derived cell line (J. Biol. Chem., 270: 20717-20723, 1995). Later, however, it was known that the CAPRIN-1 gene sequence in this report was incorrect, and in the gene sequence, deletion of a single nucleotide from the CAPRIN-1 gene sequence currently registered in the GenBank or the like causes a frame shift, thereby leading to deletion of 80 amino acids from the C terminus, and therefore the resulting artifact (74 amino acids) was the GPI-binding region mentioned in the foregoing report. In addition, it was also known that the CAPRIN-1 gene sequence shown in the report also had an error at the 5′ side, and 53 amino acid residues had been deleted from the N-terminus (J. Immunol., 172: 2389-2400, 2004). It has also been reported that the protein encoded by the CAPRIN-1 gene sequence currently registered in GenBank or the like is not a cell membrane protein (J. Immunol., 172: 2389-2400, 2004).
Based on the report of J. Biol. Chem., 270: 20717-20723, 1995, that CAPRIN-1 is a cell membrane protein, US 2008/0075722 and WO 2005/100998 describe that CAPRIN-1 can be a target of cancer therapy as a cell membrane protein under the name of M11S1. However, they do not include any specific descriptions in the Examples. As reported in J. Immunol., 172: 2389-2400, 2004, however, it has been heretofore accepted since US 2008/0075722 was filed that CAPRIN-1 is not expressed on a cell surface. It is apparent that the disclosures of US 2008/0075722 and WO 2005/100998 based only on the incorrect information that CAPRIN-1 is a cell membrane protein should not be understood as general technical knowledge in the art. In addition, there is no report that the expression level of CAPRIN-1 is higher in cancer cells such as breast cancer cells than in normal cells.